Recent studies have provided evidence that behavioral and neuronal responses to noxious stimuli are attenuated by the electrical, physiological or pharmacological stimulation of vagal afferent nerves. However, a number of important issues remain to be resolved. For example, the anatomical origin of vagal afferents that impair nociceptive reflexes has not been identified. In addition, the ability of vagal afferent nerve stimulation to specifically impair responses to noxious stimuli without impairing: 1) responses to innocuous stimuli and 2) meteoric capabilities has not been evaluated. A series of reflex studies are proposed that examine the ability of vagal afferents, which arise from different peripheral sites, to selectively modulate the digastric muscle reflex elicited by intense tooth-pulp stimulation. The effects of vagal afferent nerve stimulation on the digastric reflex produced by a putative innocuous stimulus or by direct central stimulation of the reflex will also be examined. And finally, the ability to disassociate the effects of vagal afferent nerve stimulation on the digastric reflex from reflex cardiovascular responses will be examined. A second series of single unit electrophysiological studies will examine the ability of vagal afferent nerve stimulation to alter neuronal responses of functionally classified trigeminal nucleus oralis and caudalis neurons to controlled noxious and innocuous stimuli. Cells will be classified with respect to their responses to noxious and innocuous stimuli and classified as low threshold, wide-dynamic-range or nociceptive specific neurons. Cells will also be classified as trigeminothalamic projection neurons or as non-projection neurons using standard electrophysiological procedures. The ability of vagal afferent nerve stimulation to differentially alter the responses of neurons that project to different regions of the thalamus (e.g. central medial posterior vs. medial) will be examined. These studies will more precisely define the relationship between vagal afferent nerve activity and nociception. The outcomes of these and other related studies will advance our understanding of endogenous pain modulatory networks and may lead to the development of novel strategies for controlling pain.